PubMed Health⌕ Search

Biomedical subjects

O Pignataro

Publications and source records attributed to O Pignataro.

At least 19 recordsLinked to original sources
PubMed2004

Nicergoline in the treatment of dizziness in elderly patients. A review.

In elderly patients, dizziness occurs very frequently with significant effects on the patient's life. Its frequency increases with age, and may arise from a variety of causes. Chronic dysequilibrium in elderly patients is most probably related to disturbances within the central nervous system, due either to altered neuronal functions or to an underlying vascular disease. Nicergoline, a drug used in the treatment of cognitive disturbances in geriatric patients, improves dizziness in elderly demented and non-demented patients. In a double blind,placebo controlled trial the drug improved (i) the severity of symptoms, measured by the dizziness assessment rating scale (DARS), (ii) the overall clinical conditions revealed by global impression scale, and (iii) the perceived quality of life estimated by the dizziness handicap inventory (DHI). These results indicate a possible positive effect also on posturographic measures. Moreover, the improvement occurred at no expense of the established strategy of postural control suggesting that the effect is mediated by a substitute compensatory mechanism allowing the patient to preserve consolidated postural strategies. The results of previous open clinical studies in about 3000 patients are in agreement with those findings. Overall, severity of symptoms decreased by 68 % (57 % in the control study). Globally, the results indicate a beneficial effect of nicergoline on symptoms related to balance disorders of central origin. Animal studies show that the drug displays a broad spectrum of actions on cellular and molecular mechanisms. Moreover, animal research specifically aimed at vestibular pathophysiology has revealed that nicergoline improves vestibular compensation in models of vestibular lesion. Chronic treatment with nicergoline improved the time-course of behavioral recovery in old rats after hemi-labyrinthectomy and counteracted the regulation of cholinergic receptors observed after lesion in old rats. Nicergoline interacts at several levels by various mechanisms, from the molecular level to cognitive function, probably enhancing spontaneous plasticity phenomena underlying the central vestibular compensation. This effect is not dependent from the interaction with a single-transmitter-identified neural pathway, but from anatomical, functional and neurochemical synergistic adjustments in several brain areas.

Aged↗
PubMed2001

GABA(B) receptors in anterior pituitary cells. Mechanism of action coupled to endocrine effects.

The activation of pituitary GABA(B) receptors by the specific agonist baclofen inhibits pituitary hormone secretion in vitro. Here we studied the mechanism of action of GABA(B) receptors in rat adenohypophysis. Anterior pituitary cells were obtained by trypsinization and were either plated for hormonal studies and cAMP determination or incubated in FURA 2AM for calcium measurements. Baclofen (BACL: 1 x 10(-5) M) significantly inhibited basal and thyrotropic releasing hormone (TRH)-stimulated (1 x 10(-7) M) PRL secretion in anterior pituitary cells from proestrous rats. In the presence of pertussis toxin (PTX: 150 ng/ml, 20 h), which leads to the uncoupling of the G(i/o)-protein from the receptor, both effects of BACL were abolished while the effect of dopamine (DA: 1 x 10(-8) M), used as an inhibitory control, was reduced from 70 to 25%. PTX also reversed BACL-induced inhibition of gonadotropin-releasing hormone (GnRH)-elicited luteinizing hormone (LH) secretion in anterior pituitary cells from 15-day-old female rats. In addition, though working in a pituitary mixed cell population, in which only some cell types possess GABA(B) receptors, BACL (1 x 10(-5) M) attenuated the forskolin-induced (0.5 microM) increase in cAMP. This effect was prevented by co-incubation with the antagonist 2 hydroxysaclofen and by preincubation with PTX. BACL (5 x 10(-5) M) and DA (5 x 10(-7) M) inhibited basal intracellular calcium concentrations ([Ca(2+)](i)) in pituitary cells and the effect of the latter was significantly stronger. The effect of BACL on [Ca(2+)](i) was abolished after preincubation with PTX. In the presence of the potassium channel blocking agents barium (200 microM and 1 mM) and tetraethylammonium (10 mM), BACL was still able to inhibit [Ca(2+)](i). Blockade of voltage-sensitive calcium channels (VSCC) with either verapamil (5 x 10(-6) M) or nifedipine (1 x 10(-6) M) completely abolished the effect of BACL on [Ca(2+)](i). In the presence of 12.5 mM potassium concentration baclofen significantly inhibited [Ca(2+)](i). In conclusion, our results describe the negative coupling of adenohypophyseal GABA(B) receptors to VSCC through PTX-sensitive G-proteins. These characteristics suggest a resemblance of these receptors to the typical presynaptic GABA(B) sites described in the central nervous system.

Animals↗
PubMed1999

Alpha2-adrenergic effect on human breast cancer MCF-7 cells.

(-)Epinephrine (Epi) and (-)Norepinephrine (NEpi) significantly stimulated tritiated Thymidine incorporation in MCF-7 cells at concentrations 10-30pM to 10nM, with an EC50 of 10pM for Epi and 14.2pM for NEpi. To characterize this action, cells were incubated in the presence of NEpi or Epi and different antagonists. The beta-adrenergic antagonist Propanolol showed no effect on the agonist's stimulation, whereas the alpha-adrenergic antagonist Phentolamine, reverted it completely at high concentrations (100 microM). The alpha1-adrenergic antagonist Prazosin (Pra) acted only at high concentrations, while the alpha2-adrenergic antagonist Yohimbine (Yo) reverted the stimulation at an EC50 of 0.11 microM. Likewise, when the cells were incubated in the presence of the specific alpha2-adrenergic agonist Clonidine (Clo), Thymidine incorporation was significantly stimulated at an EC50 of 0.298 pM. Again, the incubation of the cells in the presence of the alpha1-adrenergic antagonist Pra exerted its action at high concentrations, whereas the alpha2-adrenergic antagonist Yo showed a clear reversal of the agonist's enhancement at an EC50 of 0.136 microM. Moreover, Clo caused a clear and significant inhibition of stimulated cAMP levels both in the intracellular and the extracellular fractions. Yo showed a complete reversion of cAMP levels to control values in the presence of Clo, while Pra had the opposite effect. These data suggest that the stimulation provoked in Thymidine incorporation by the agonists Epi, NEpi, and Clo is, at least in part, due to an alpha2-adrenergic mechanism directly on tumoral cells, and that the effect is coupled with inhibition of cAMP levels, as described for this kind of receptors.

Adrenergic alpha-Agonists↗
PubMed1998

Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat model of chronic renal failure.

Chronic renal failure (CRF) is accompanied by adaptive changes in electrolyte reabsorption in the thick ascending limb of Henle of surviving nephrons. To study the cellular mechanism of this adaptation, we measured intracellular cAMP in micro-dissected medullary thick ascending limb (mTAL) segments in rats with CRF. mTAL exhibited in CRF an increase of basal cAMP from 25.6 +/- 10.0 in controls to 65.8 +/- 11.3 fmol mm-1 tubule in CRF (P < 0.05). Vasopressin and calcitonin stimulated mTAL adenylate-cyclase in a dose-dependent manner in controls but failed to stimulate in CRF. Likewise, maximal stimulation with 10(-3) M 3-isobutyl-1-methylxanthine (IBMX) plus 10(-5) M forskolin increased cAMP in controls to 63.0 +/- 16.0 but not in CRF, where maximal stimulated values remained at 63.1 +/- 18.8 fmol mm-1 tubule (P NS). Alpha2-adrenoreceptor activation with clonidine at concentrations ranging from 10(-8) to 10(-6) M diminished cAMP production by 37% in CRF (P < 0.05), whereas no differences were found in controls. Thus, the basal intracellular cAMP is increased in rat mTAL in CRF. The finding that neither forskolin nor vasopressin were able to further augment intracellular cAMP would suggest that stimulatory pathways of the adenylate-cyclase system are activated in the basal state. However, mTAL cells in CRF seem to retain the response of normal epithelium to inhibitory pathways such as the one mediated by alpha2-adrenoreceptors.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Role of cyclic 3'5' guanosine monophosphate and nitric oxide in the regulation of iodide uptake in calf thyroid cells.

Sodium nitroprusside (SNP) spontaneously produces nitric oxide (NO). In many cell types, this activates the soluble form of the enzyme guanylyl cyclase (GC), resulting in the elevation of cGMP. We herein report the role of NO and cGMP on iodide uptake in primary cultures of calf thyroid cells. Iodide uptake is the limiting step in thyroid hormone biosynthesis and a typical functional parameter. The effect of SNP on this parameter was thus determined. In cells treated with TSH for 72 h, addition of 5 mM SNP for the last 2 h caused a significant inhibition on iodide uptake, with no change in cells not treated with TSH. This action was mimicked by an analogue of cGMP, 8Br-cGMP, and blocked by reduced hemoglobin, thus suggesting that it is mediated by the GC-cGMP pathway. SNP also inhibited the stimulation caused by forskolin or analogues of cAMP, indicating that the effect takes place in this pathway, which would be distal to cAMP generation. The accumulation of radioiodine by thyroid cells is a consequence of the balance between influx and efflux. The studies demonstrate that SNP does not affect iodide efflux, thus revealing that it inhibits the influx.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

DA1 and DA2 receptor regulation in the striatum of young and old rats after peripheral vestibular lesion.

Anatomical, lesion and functional studies have indicated that the mesostriatal dopaminergic (DAergic) system may serve as supravestibular center in posture and locomotion control. Nevertheless, no data are available on the involvement of DAergic systems during vestibular compensation. This study was designed for the analysis of DA1 and DA2 receptors in the striatum by means of quantitative receptor autoradiography 28 days after unilateral or bilateral lesion of the labyrinth in 3-month-old rats. Considering the severe decline of DA content and receptors in striatum and the difference in behavioral recovery after vestibular lesions in old age, we also analyzed 24-month-old, lesioned and unlesioned rats. In young rats, hemilabyrinthectomy caused a bilateral increase (20-30%) of DA1 receptors and a two-fold increase of DA2 receptors. In old-rats, we observed a similar modification of DA2 receptors, and a 50% increase in DA1 receptors. Bilabyrinthectomy did not modify DA1 receptor density and decreased DA2 receptor density in young animals, whereas it produced an increase in both DA1 and DA2 in old rats. This study provides evidence for the involvement of the DAergic system during vestibular compensation. Our results also indicate great biochemical plasticity of the remaining DA receptors in the striatum of old rats.

Aging↗
PubMed1996

Otitis media with effusion and S-carboxymethylcysteine and/or its lysine salt: a critical overview.

An overview of the placebo-comparative articles retrieved by a literature search on Medline - Embase - Biosis data banks from 1972 to 1993 was performed to evaluate the therapeutic relevance of the medical treatment with S-carboxymethylcysteine (SCMC) and its monohydrate lysine salt (SCMC-LYS) in patients with otitis media with effusion (OME). Ten original published studies were reviewed by an independent physician who assessed their quality by standard nine-items methodology. A meta-analytical approach was used to compare outcomes across all qualifying studies. Because of the heterogeneity of clinical endpoints, a new outcome measure was defined, i.e. overall clinical improvement, which consisted of the number of patients with complete resolution of clinical signs and symptoms and no need for surgical intervention. The objective evaluation criteria of normalisation of tympanogram was an additional end-point. Potential confounding variables such as eligibility criteria, treatment protocol and study design of the six methodologically complying studies were statistically homogeneous. No association was found between treatment effect-size and publication date or patients' age. Outpatients with disease duration of < 6 months, not previously treated, with bilateral ear involvement were included in the studies; half of them presented hyperplasia or hypertrophy of the pharyngeal or the adenoid tissue. Out of 483 patients, 430 (89%) terminated studies and were evaluable. Results from this meta-analysis indicate that patients with OME receiving oral SCMC/-lys benefit from the medical treatment to the extent of avoiding surgical intervention approximately 2.31 times more often than similar patients receiving placebo (ratio of active drug to placebo-effect on overall clinical improvement: 2.31; C.I. 1.28-4.20, P < 0.01) and attain reversion to normal of the tympanogram at an extent close to statistical significance (odds ratio: 2.25, C.I. 0.97-5.22, P = 0.058). In conclusion, the use of this new methodology for the evaluation of the mucoactive drug effect in OME has shed light into methodological pitfalls of clinical trials to date and underlines the need for agreed outcome measures, which may modify medical policy, which addresses more and more often to symptomatic treatment.

Adolescent↗
PubMed1995

Cellular adaptation of the rat medullary thick ascending limb to chronic renal failure.

Chronic renal failure (CRF) is accompanied by adaptive changes in renal and extrarrenal epithelial ionic transport. Fluid reabsorption in the thick ascending limb of Henle is increased and the capacity to lower the urine osmolality in water diuresis is preserved. To study the cellular mechanism of this adaptation, we measured intracellular cAMP in microdissected medullary thick ascending limb (mTAL) segments in rats with CRF. mTAL exhibited in CRF nephrons an increase of basal cAMP from 6.0 +/- 1.5 in controls to 47.0 +/- 10.3 fmol. mm-1 tubule in CRF (P < 0.05). Maximally stimulated cAMP levels (10(-3) M IBMX plus 10(-5) M Forskolin) were different from basal levels in controls (6.0 +/- 1.5 vs 63.1 +/- 18.8, P < 0.05) but not from basal levels in CRF (47.0 +/- 10.3 vs 63.0 +/- 16.0, P = N.S.). Preincubation with the adenylate cyclase inhibitor 2'5'-dideoxyadenosine (DDA) 10(-4) M produced no changes in cAMP in controls (93.7 +/- 10.3% of DDA untreated samples) whereas it decreased to 76.2 +/- 8.8% (24% inhibition) in CRF (P < 0.05). No differences between controls and CRF groups were found in basal and stimulated cAMP in red blood cells and distal colon. The data would suggest that the cAMP pathway is an intracellular signal for mTAL adaptation in epithelial transport and that the adenylate-cyclase system is specifically activated in CRF.

Animals↗
PubMed1993

Early cell cycle diacylglycerol (DAG) content and protein kinase C (PKC) activity enhancement potentiates prostaglandin F2 alpha (PGF2 alpha) induced mitogenesis in Swiss 3T3 cells.

R59022, a diacylglycerol kinase inhibitor, enhances the prostaglandin F2 alpha (PGF2 alpha)-induced diacylglycerol (DAG) synthesis in Swiss 3T3 cells. It also potentiates the PGF2 alpha-mediated protein kinase C (PKC)-dependent 80 kDa protein (80K) phosphorylation and initiation of DNA replication. R59022 enhances the PGF2 alpha mitogenic response by increasing the rate of entry into the S phase. Insulin does not cause 80K phosphorylation, and does not enhance its induction but it potentiates the PGF2 alpha mitogenic response. These results suggest that mitogenically triggered fluctuations in DAG content and PKC activity play a pivotal role in controlling the PGF2 alpha-induced DNA synthesis while insulin acts via a different mechanism.

3T3 Cells↗
PubMed1992

Increased activity of type I regulatory subunit of cyclic adenosine 3',5'-monophosphate-dependent protein kinase in estrogen-induced pituitary tumors.

BACKGROUND: Previous studies have shown that binding of [3H]cyclic adenosine 3',5'-monophosphate (cAMP) is increased in cytosol of diethylstilbestrol (DES)-induced pituitary tumors. In tumor cells, the cAMP-binding proteins that stimulate cell proliferation have been shown to predominate over those that inhibit it. PURPOSE: This study was designed to determine the type of regulatory subunit (R) of cAMP-dependent protein kinase (PK) responsible for this binding by determining the type of subunit that is increased in DES-induced pituitary tumors. METHODS: Experiments were carried out on three groups of Fischer 344 rats: 1) rats with DES-induced pituitary tumors, 2) ovariectomized rats receiving short-term estrogen treatment with estradiol benzoate (E2) for 4 days, and 3) ovariectomized control rats. We performed immunoprecipitation of RI and RII subunits with polyclonal antibodies in pituitary cytosol (direct method) or after separation of subunits by DEAE-cellulose chromatography (indirect method). The concentration of cAMP was also quantified by radioimmunoassay in pituitaries from the three groups. RESULTS: Direct immunoprecipitation with RI antibody demonstrated a statistically significant increase in [3H]cAMP bound to RI in rats receiving E2 for 4 days over that for control rats and an even more significant increase in rats with DES-induced pituitary tumors. There was little change in the nucleotide [3H]cAMP bound to RII. Immunoprecipitation of the eluted fractions after chromatography demonstrated an RI subunit in peaks 1 and 2, whereas RII was contained almost exclusively in peak 2. After chromatography (indirect method), immunoprecipitation with RI and RII antibody indicated an overall increase in the level of binding to RI protein in tumors. Levels of cAMP in DES-induced pituitary tumors were also high compared with levels in controls or in glands from estrogen-treated rats. CONCLUSIONS: In DES-induced pituitary tumors, cAMP may be preferentially bound to one isozyme of PK, which supports current theories that cell proliferation and tumor growth correlate with high expression of the RI subunit. IMPLICATIONS: We plan studies to investigate the effects on tumor growth of the site-selective analogue 8-chloro-cAMP, which binds to RII and causes the elevated levels of the RI subunit of the tumor cells to return to normal levels.

Analysis of Variance↗
PubMed1986

Human pharmacokinetics and distribution in various tissues of ceftriaxone.

Multiple-dose pharmacokinetics of ceftriaxone were investigated in 7 patients with bronchopneumonia using an intramuscular regimen of 1 g given every 24 h for 7 days. Serum, sputum, and urine samples were collected serially following the first dose (day 1) and last dose (day 7). Mean peak serum concentrations of ceftriaxone occurred at 2 h on both days and were 67.8 and 75.1 micrograms/ml, respectively, on day 1 and day 7. Ceftriaxone had a half-life of 6.9 h on day 1 and 7.4 h on day 7. The half-life of ceftriaxone in sputum was 5.9 and 6.6 h, respectively, on days 1 and 7. Approximately 50% of the dose of ceftriaxone was recovered in the urine within 24 h on day 1, 60% on day 7. Tissue distribution of ceftriaxone was determined in 103 patients following intramuscular administration of a single 1-gram dose at different times up to 24 h prior to surgery. High concentrations of ceftriaxone were found in lung, tonsil, middle ear mucosa, and nasal mucosa, and therapeutic levels of ceftriaxone persisted for 24 h after administration.

Ceftriaxone↗
PubMed1984

Functional neck dissection: an evaluation and review of 843 cases.

After briefly reviewing the principles, indications, and merits of functional neck dissection, the results of 1200 neck dissections performed on 843 patients in the period 1961-1979 are presented. They compare very favorably with those reported for classic (radical) neck dissection by other leading authors; however, a retrospective analysis of data derived from material of different origin is hardly possible and has a disputable value. Therefore, we decided to compare our data on functional neck dissections (FND) with those of classic neck dissections (CND) performed by the same surgical team at the same clinic in the period 1948-1960. The clinical material was largely the same in both cases, and the data were collected and analyzed using the same criteria. In both series, neck dissections were divided into elective and curative. It could be demonstrated that the number of neck recurrences observed in the dissected necks is the same for FND and CND in curative dissections, while it is considerably lower for FND in elective neck dissections. This of course does not prove improved radicality in FND, but only proves that a systematic bilateral elective neck dissection in N0 cases affords improved cancerological safety. This radical bilateral approach to regional lymph nodes is made possible routinely by FND which avoids the problems of unnecessary mutilation. The figures produced speak in favor of a wider adoption of FND especially for expanding the indications to elective treatment of regional lymph nodes in cancer of the head and neck. Elective neck dissection is made practically harmless by this newer technique and averts the dreadful appearance of late metastases in N0 cases.

Head and Neck Neoplasms↗
PubMed1980

Functional neck dissection. A description of operative technique.

The operative technique involved in functional neck dissection is described to clarify its stepwise execution. Recent interest in functional preservation demands therapeutic techniques that are oncologically reliable but not multilating. The functional neck dissection seems to be a reasonable alternative to radical radiotherapy and a preferred alternative to traditional neck dissection in the control of regional metastasis when disease in the neck is either occult of still confined to mobile lymph nodes.

Head and Neck Neoplasms↗
PubMed1979

The evolution of the vestibular apparatus according to the age of the infant.

In 56 full-tem A.G.A. infants and in 27 infants of a minimal age of 15 days with a neurological "risk" (full-term small for gestational age, S.G.A.), the nystagmic response to vestibular stimulation (rotatory and torsion swing test) was examined. A delay in the appearance of a response to the labyrinthic stimulus and a persistence of the prevalence of the slow phase of the nystagmus appeared clearly higher in the "risk" infants. The statistical difference of the response between the two groups was highly significant. This allowed us to conclude that the vestibular test appears to the one of the most useful in evaluating the sensorial maturation of S.G.A. infants.

Electronystagmography↗